Effect of alfacalcidol on natural course of renal bone disease in mild to moderate renal failure

BMJ 1995;310:358-363 (11 February)

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Effect of alfacalcidol on natural course of renal bone disease in mild to moderate renal failure

Neveen A T Hamdy, clinical research fellow,^a John A Kanis, professor,^a Monique N C Beneton, research assistant,^a Colin B Brown, consultant physician,^b Job R Juttmann, physician,^c Johannes G M Jordans, physician,^d Sylvie Josse, physician,^e Alain Meyrier, professor,^f Robert L Lins, physician,^g Ian T Fairey, clinical data manager ^h

^a WHO Collaborating Centre for Metabolic Bone Diseases, Department of Human Metabolism and Clinical Biochemistry, University of Sheffield Medical School, Sheffield S10 2RX, ^b Department of Renal Medicine and Transplantation, Northern General Hospital, Sheffield S5 7AU, ^c Department of Internal Medicine, Sint Elisabeth Ziekenhuis, NL-5002 Tilburg, Netherlands, ^d Department of Internal Medicine (Nephrology), Medisch Spectrum Twente, NL-7511, Enschede, Netherlands, ^e Service de Nephrologie, Hopital Du Bois Guillaume, BP100, F-76233, Bois Guillaume, France, ^f Service de Nephrologie, Hopital Avicenne, F-93000, Bobigny, France, ^g Nephrologie, Stuivenberg Algemeen Ziekenhuis, B-2000 Antwerpen, Belgium, ^h Leo Laboratories, Princes Risborough HP27 9RR

Correspondence to: Professor Kanis.

Abstract

Objective: To determine whether alfacalcidol--used in managementof overt renal bone disease--may safely prevent renal bone diseasewhen used earlier in course of renal failure.
Design: Double blind, prospective, randomised, placebo controlledstudy.
Setting: 17 nephrology centres from Belgium, France, the Netherlands,and the United Kingdom.
Subjects: 176 patients aged 18-81 with mild to moderate chronicrenal failure (creatinine clearance 15-50 ml/min) and with noclinical, biochemical, or radiographic evidence of bone disease.
Interventions: Alfacalcidol 0.25 µg (titrated accordingto serum calcium concentration) or placebo given for two years.
Main outcome measures: Quantitative histology of bone to assessefficacy of treatment and renal function to assess safety.
Results: 132 patients had histological evidence of bone diseaseat start of study. Biochemical, radiographic, and histologicalindices of bone metabolism were similar for the 89 patientsgiven alfacalcidol and the 87 controls given placebo. Aftertreatment, mean serum alkaline phosphatase activity and intactparathyroid hormone concentration had increased by 13% and 126%respectively in controls but had not changed in patients givenalfacalcidol (P<0.001). Hypercalcaemic episodes occurredin 10 patients given alfacalcidol (but responded to decreasesin drug dose) and in three controls. Histological indices ofbone turnover significantly improved in patients given alfacalcidoland significantly deteriorated in controls: among patients withabnormal bone histology before treatment, bone disease resolvedin 23 (42%) of those given alfacalcidol compared with two (4%)of the controls (P<0.001). There was no difference in rateof progression of renal failure between the two groups.
Conclusion: Early administration of alfacalcidol can safelyand beneficially alter the natural course of renal bone diseasein patients with mild to moderate renal failure.

Key messages

Key messages
Treating such patients with alfacalcidol (up to 1 µg/day for two years) significantly improved their osteomalacia and hyperparathyroid disease
Treatment had no apparent adverse effect on renal function
Hypercalcaemic episodes were uncommon and readily responded to decreases in drug dose
Alfacalcidol might be used more widely for patients with moderate renal failure not yet needing dialysis

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